ArticlePloS one2018
Enhanced susceptibility to stress and seizures in GAD65 deficient mice.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- A compact GAD67 promoter enables inhibitory neuron-targeted AAV gene therapy for seizure suppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
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- Exercise Ameliorates Fluoride-induced Anxiety- and Depression-like Behavior in Mice: Role of GABA.Biological trace element research · 2022Article
- Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: A postmortem study.Progress in neuro-psychopharmacology & biological psychiatry · 2022Article
- Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders.Frontiers in cellular neuroscience · 2022Review
- Impact of Dysfunctional Feed-Forward Inhibition on Glutamate Decarboxylase Isoforms and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Article
- Optogenetic stimulation of kisspeptin neurones within the posterodorsal medial amygdala increases luteinising hormone pulse frequency in female mice.Journal of neuroendocrinology · 2020Article
- Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice.Scientific reports · 2019Article
- EGF Treatment Improves Motor Behavior and Cortical GABAergic Function in the R6/2 Mouse Model of Huntington's Disease.Molecular neurobiology · 2019Article
- Sex- and age-related changes in GABA signaling components in the human cortex.Biology of sex differences · 2019Article
- Protective Role of L-3-Frontiers in pharmacology · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.
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